The internal mammary artery, also known as the internal thoracic artery, perfuses the anterior chest wall and mammary glands. The internal mammary artery has a superior, long-term patency compared to saphenous vein grafts, and is regarded as the primary vessel of choice for coronary artery bypass grafting. Compared to coronary and carotid arteries, the mammary artery is highly resistant to arthrosclerosis. This long-term resistance of the internal mammary artery to graft atherosclerosis, compared with the saphenous vein has been attributed, at least in part, to its superior endothelial cell function. In addition, the response of the internal mammary artery to mechanical injury is also different from that of coronary arteries. Human coronary arteries respond to balloon angioplasty by promoting cell migration and proliferation, leading to the formation of neointima and restenosis in approximately 40% of cases. However, unlike coronary arteries and saphenous vein graft, restenosis was not found in internal mammary artery grafts after percutaneous transluminal angioplasty. Therefore, the internal mammary artery could be a valuable tissue source for vascular progenitor cells.
It has been well documented that ectopic tissue, composed of cartilage, bone, and fat, is able to form within the wall of arteries. This phenomenon is termed metaplasia and suggests that multipotential progenitor cells may reside within the arterial wall. Osteogenic and chondrogenic differentiation within the artery wall is recognized clinically as vascular calcification and this type of mineralization is associated with increased cardiovascular injury. Vascular calcification is known to increase aortic stiffness, resulting in systolic hypertension, coronary insufficiency, left ventricular hypertrophy, ischemia, and congestive heart failure. In fact, approximately 85% of plaques causing coronary thrombosis are calcified. It has been suggested that progenitor cells within the artery wall might play a role in plaque formation, calcification and arthrosclerosis. Therefore understanding how these cells contribute to vascular pathology, as well as repair might lead to improved therapies for cardiovascular indications.
Many laboratories are currently focused on understanding the role of stem cells in vascular physiology. It has been shown that adult organs contain stem cells that are involved in organ maintenance and repair after injury. Therefore, it is feasible that adult progenitor cells can be isolated from many, if not all types of organ tissue. These tissue-specific progenitor cells could then be exploited for tissue-specific therapeutic purposes.
Zingin et al., recently demonstrated the existence of a ‘vasculogenic zone’ in the adult human vascular wall. In this study, putative progenitor cells were isolated from human internal thoracic arteries. To harvest the cells, arteries were minced and digested with trypsin/EDTA at 37° C. for 5 minutes. Non-digested tissues were removed by filtration. The suspension was centrifuged and the resulting cell pellet was resuspended into endothelial growth culture medium and plated onto collagen or fibronectin-coated dishes. These cells demonstrated the expression of CD34. Progenitor cells, expressing KDR/Flk1 and CD45 were also shown to be present within the vascular wall of the internal mammary artery. These data suggest that there is a pool of progenitor cells within the wall of the internal mammary artery.
The identification and isolation of a vascular wall progenitor cell that is manufacturable and resistant to atherosclerosis might prove to be beneficial for cell therapy and tissue engineering applications. In an attempt to harness the internal mammary artery's unique anti-atherogenic and mechanical attributes, we have isolated and characterized unique progenitor cells from human internal mammary arteries and evaluated their utility in tissue engineering applications.